Immunohistochemical studies using surgically resected specimens from colorectal cancer patients and esophageal cancer patients indicated that the VEGF expression by the tumor cells and its receptor KDR expression by the endothelial cells correlated with the microvessel density (MVD), and that the VEGF expression or its combined expression with KDR might be an independent prognostic factor. We also found a correlation between the ETS- 1 expression by the endothelial cells, and the VEGF and pyrirnidine nucleotide (PyNPase) expression in colorectal cancer. Moreover, the ETS- 1 expression was found to be an independent prognostic factor in colorectal cancer.The expression of transcription factor ETS-1 was induced in endothelial cells (HOMEC) by bFGF. Differential display and western blot analysis showed that ETS-1 induced u-PA and MMP-l that related with angiogenesis. ETS-1 was found to induce gp96 mRNA in HOMEC.These results suggested that ETS-l might be candidate as a target molecule for anti-angiogenic therapy. We have to evaluate a significance of heat shock protein gp96 in relation to angiogenesis.血管内皮細胞(HOMEC)をbFGFで刺激するとETS-1 mRNAおよび蛋白が発現した.ets-1アンチセンスオリゴヌクレオシドによりその発現はほぼ抑制された.differential display(DD)の結果,ETS-1発現細胞には非発現細胞にみられない数種類のPCR産物が認められ,クローニング後の塩基配列よりu-PA, MMP-1,さらに熱ショック蛋白gp96遺伝子と確認された.ウェスタンブロットによりbFGFで刺激したHOMECではこれら蛋白の産生増強が確認された.血管新生因子bFGFは血管内皮細胞に対し転写因子ETS-1を介してu-PAやMMPなど血管新生関連分子を産生誘導することが示唆された.(結語)腫瘍血管内皮細胞に発現するETS-1は抗血管新生療法における分子標的となる可能性がしさされた.ETS-1により誘導されるストレス蛋白gp96の血管内皮細胞における意義,とくに血管新生との関連については今後の課題である.